Die Auswirkungen des Tacrolimusspiegels und dessen Schwankung nach Lungentransplantation auf das Überleben der Patienten

Klaubert, Niklas (2022): Die Auswirkungen des Tacrolimusspiegels und dessen Schwankung nach Lungentransplantation auf das Überleben der Patienten. Dissertation, LMU München: Medizinische Fakultät

Abstract

In transplant medicine Tacrolimus has established as an effective drug for immune suppression. Whereas plenty of data concerning dosage and side effects is available for common medical interventions such as kidney transplantation, scientific knowledge concerning immune suppression in lung transplantation (LTx) is limited due to a lack of data. The objective of this research is to investigate the dosage-response relationship of Tacrolimus in patients with lung transplantation as well as relevant side effects such as nephrotoxicity. Therefore, 100 patients with immune suppression after LTx were classified into two major groups depending on the quantity of Tacrolimus drug levels. Further, the effect of level fluctuation was investigated. Data inquisition included drug levels within the first 12 months after LTx as well as kidney and pulmonary function after 24 months. Further, survival after 36 months as well as overall survival were analyzed. Epidemiological factors such as age and gender as well as past medical history and the type of medical intervention concerning LTx were relevant variables for outcome analysis. The results indicate that higher Tacrolimus drug levels in blood correlate with a significantly higher three-year and overall survival rate as well as prevention of developing chronic transplant failure. Further findings demonstrate a better outcome for patients with reduced overall level fluctuations. Concerning nephrotoxicity, in all patients a deterioration of kidney function was observed, independently of the quantity of administered Tacrolimus. Age, gender, pre-existing conditions and type of intervention showed no relevant prognostic significance. In a synopsis of all data, it can be concluded that the risk of pulmonary failure after lung transplantation can be decreased by sufficiently high Tacrolimus drug levels with minimized level fluctuation. Thus, high Tacrolimus levels correlate with better transplant outcome. Fluctuating drug levels with exceeded or undercut therapeutic index result in less efficient prevention of rejection reaction. This might be caused either by low drug levels with insufficient immunosuppressant effects or by exceedance of the therapeutic range and thus relevant side effects such as nephrotoxicity with consecutive dosage reduction. Based on these results, Tacrolimus drug levels after LTx should be kept steady within the upper target range. Level fluctuations should be avoided by considering close-meshed monitoring, optimized patient compliance as well as adjustment of drug administration to the patients’ individual requests.

• Dokumententyp: Dissertationen (Dissertation, LMU München)
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften ; 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• Fakultäten: Medizinische Fakultät
• Sprache der Hochschulschrift: Deutsch
• Datum der mündlichen Prüfung: 10. November 2022
• 1. Bericht­erstatter:in: Kneidinger, Nikolaus